Positive and negative modulation of group I metabotropic glutamate receptors

被引：47

作者：

Vanejevs, Maksims ^{[1
]}

Jatzke, Claudia ^{[2
]}

Renner, Steffen ^{[2
]}

Mueller, Sibylle ^{[2
]}

Hechenberger, Mirko ^{[2
]}

Bauer, Tania ^{[2
]}

Klochkova, Anna ^{[3
]}

Pyatkin, Ilya ^{[3
]}

Kazyulkin, Denis ^{[3
]}

Aksenova, Elena ^{[3
]}

Shulepin, Sergey ^{[3
]}

Timonina, Olga ^{[3
]}

Haasis, Ariane ^{[2
]}

Gutcaits, Aleksandrs ^{[1
]}

Parsons, Christopher G. ^{[2
]}

Kauss, Valerjans ^{[1
]}

Weil, Tania ^{[2
]}

机构：

[1] Inst Organ Synth, LV-1006 Riga, Latvia

[2] Merz Pharmaceut GmbH, D-60438 Frankfurt, Germany

[3] Asinex Ltd, Moscow 125367, Russia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 03期

关键词：

D O I：

10.1021/jm0611298

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as positive and negative mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homology model of the mGlu1 receptor was established and a putative binding mode within the receptor's transmembrane domain was visualized.

引用

页码：634 / 647

页数：14

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